Open AccessJournal Article
Myostatin (GDF-8) as a key factor linking muscle mass and bone structure.
Moataz Elkasrawy,Mark W. Hamrick +1 more
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TLDR
The data suggest that myostatin has direct effects on the proliferation and differentiation of osteoprogenitor cells, and that hisostatin antagonists and inhibitors are likely to enhance both muscle mass and bone strength.Abstract:
Myostatin (GDF-8) is a member of the transforming growth factor-beta (TGF-β) superfamily that is highly expressed in skeletal muscle, and myostatin loss-of-function leads to doubling of skeletal muscle mass. Myostatin-deficient mice have been used as a model for studying muscle-bone interactions, and here we review the skeletal phenotype associated with altered myostatin signaling. It is now known that myostatin is a key regulator of mesenchymal stem cell proliferation and differentiation, and mice lacking the myostatin gene show decreased body fat and a generalized increase in bone density and strength. The increase in bone density is observed in most anatomical regions, including the limbs, spine, and jaw, and myostatin inhibitors have been observed to significantly increase bone formation. Myostatin is also expressed in the early phases of fracture healing, and myostatin deficiency leads to increased fracture callus size and strength. Together, these data suggest that myostatin has direct effects on the proliferation and differentiation of osteoprogenitor cells, and that myostatin antagonists and inhibitors are likely to enhance both muscle mass and bone strength.read more
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Insulin Resistance and the Polycystic Ovary Syndrome Revisited: An Update on Mechanisms and Implications
TL;DR: In this paper, the authors summarized the state of the science since the last review in the Endocrine Reviews in 1997, and concluded that obese women with PCOS are insulin resistant, but some groups of lean affected women may have normal insulin sensitivity.
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TGF-β/TGF-β receptor system and its role in physiological and pathological conditions
TL;DR: The knowledge about the mechanisms involved in TGF-β signal transduction has allowed a better understanding of the disease pathogenicity as well as the identification of several molecular targets with great potential in therapeutic interventions.
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The myokine irisin increases cortical bone mass
Graziana Colaianni,Concetta Cuscito,Teresa Mongelli,Paolo Pignataro,Cinzia Buccoliero,Peng Liu,Ping Lu,Loris Sartini,Mariasevera Di Comite,Giorgio Mori,Adriana Di Benedetto,Giacomina Brunetti,Tony Yuen,Li Sun,Janne E. Reseland,Silvia Colucci,Maria I. New,Mone Zaidi,Saverio Cinti,Maria Grano +19 more
TL;DR: It is shown that a molecule irisin derived from skeletal muscle in response to exercise has profound effects in enhancing mass and improving the geometry and strength specifically of cortical bone, the key function of which is to resist bending and torsion.
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Common variants at CDKAL1 and KLF9 are associated with body mass index in east Asian populations
Yukinori Okada,Michiaki Kubo,Hiroko Ohmiya,Atsushi Takahashi,Natsuhiko Kumasaka,Naoya Hosono,Shiro Maeda,Wanqing Wen,Rajkumar Dorajoo,Rajkumar Dorajoo,Min Jin Go,Wei Zheng,Norihiro Kato,Jer-Yuarn Wu,Jer-Yuarn Wu,Qi Lu,Tatsuhiko Tsunoda,Kazuhiko Yamamoto,Yusuke Nakamura,Naoyuki Kamatani,Toshihiro Tanaka +20 more
TL;DR: A genome-wide association study and replication studies with 62,245 east Asian subjects identified two new body mass index–associated loci and an interaction between a SNP in the KLF9 locus and one in the MSTN locus should provide useful insights into the etiology of obesity.
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Bone and muscle: Interactions beyond mechanical
Marco Brotto,Lynda F. Bonewald +1 more
TL;DR: This brief review article introduces some of the key reasons why the mechanical coupling theory has dominated the authors' view of bone-muscle interactions followed by summarizing evidence for the secretory nature of bones and muscles.
References
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Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member.
TL;DR: Results suggest that GDF-8 functions specifically as a negative regulator of skeletal muscle growth, which is significantly larger than wild-type animals and show a large and widespread increase in skeletal muscle mass.
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Myostatin Mutation Associated with Gross Muscle Hypertrophy in a Child
Markus Schuelke,Kathryn R. Wagner,Leslie E Stolz,Christoph Hübner,Thomas Riebel,Wolfgang Kömen,Thomas Braun,James F. Tobin,Se-Jin Lee +8 more
TL;DR: A mutation in the gene for myostatin is described in a child with muscle hypertrophy and unusual strength and greater understanding of muscle growth and maintenance is important for future therapies.
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Induction of cachexia in mice by systemically administered myostatin
Teresa A. Zimmers,Monique V. Davies,Leonidas G. Koniaris,Paul A. Haynes,Aurora F. Esquela,Kathy Tomkinson,Alexandra C. McPherron,Neil M. Wolfman,Se-Jin Lee +8 more
TL;DR: It is shown that myostatin circulates in the blood of adult mice in a latent form that can be activated by acid treatment, and may be a useful pharmacologic target in clinical settings such as cachexia, where muscle growth is desired.
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Regulation of muscle mass by myostatin
TL;DR: The existence of circulating tissue-specific growth inhibitors of this type was hypothesized over 40 years ago to explain how sizes of individual tissues are controlled and skeletal muscle appears to be the first example of a tissue whose size is controlled by this type of regulatory mechanism.
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Differential Temporal Expression of Members of the Transforming Growth Factor β Superfamily During Murine Fracture Healing
TL;DR: Bone morphogenetic protein 2 (BMP‐2) and growth and differentiation factor 8 (GDF8) showed maximal expression on day 1 after fracture, suggesting their roles as early response genes in the cascade of healing events, and restricted expression of GDF8 to day 1 suggests that it may similarly regulate cell differentiation early in the fracture healing process.